RNA-Specific Oligonucleotide

Antisense oligonucleotides are under intense investigation as novel therapeutics for sequence specific regulation of gene expression. We have designed and incorporated an internucleotidic linkage as part of an oligonucleotide structure that retains the base-recognition properties, aqueous solubility and achirality of natural deoxyoligonucleotides. An octamer was prepared via solid phase phosphoramidite methodology using standard reagents and protocols. Initial binding studies indicate thermal stability to complementary RNA comparable to the natural cogener. Interestingly, no binding to complementary DNA was detected suggesting a new class of RNA specific hybridization agents. We will synthesize the necessary cyanoethylphosphoramidites and derivatized supports in order to prepare oligomers for additional hybridization and nuclease stability studies. Future work will focus on the synthesis and evaluation of antisense oligonucleotides containing this internucleotidic linkage to inhibit protein synthesis in a cell culture model system.